Analysis of Multiple Drug Resistance Mechanism in Different Types of Soft Tissue Sarcomas: Assessment of the Expression of ABC-Transporters, MVP, YB-1, and Analysis of Their Correlation with Chemosensitivity of Cancer Cells.

Chemotherapy of soft tissue sarcomas (STS) is restricted by low chemosensitivity and multiple drug resistance (MDR). The purpose of our study was the analysis of MDR mechanism in different types of STS. We assessed the expression of ABC-transporters, MVP, YB-1, and analyzed their correlation with chemosensitivity of cancer cells. STS specimens were obtained from 70 patients without metastatic disease (2018-2020). Expression level of MDR-associated genes was estimated by qRT-PCR and cytofluorimetry. Mutations in ABC-transporter genes were captured by exome sequencing. Chemosensitivity (SI) of STS to doxorubicin (Dox), ifosfamide (Ifo), gemcitabine (Gem), and docetaxel (Doc) was analyzed in vitro. We found strong correlation in ABCB1, ABCC1, and ABCG2 expression. We demonstrated strong negative correlations in ABCB1 and ABCG2 expression with SI (Doc) and SI (Doc + Gem), and positive correlation of MVP expression with SI (Doc) and SI (Doc + Gem) in undifferentiated pleomorphic sarcoma. Pgp expression was shown in 5 out of 44 STS samples with prevalence of synovial sarcoma relapses and it is strongly correlated with SI (Gem). Mutations in MDR-associated genes were rarely found. Overall, STS demonstrated high heterogeneity in chemosensitivity that makes reasonable in vitro chemosensitivity testing to improve personalized STS therapy, and classic ABC-transporters are not obviously involved in MDR appearance.

Occupational Safety in Chemosensitivity Tests: A Method to Minimize the Risk of Contamination While Maximizing the Safety for the Examiner.

In vitro chemosensitivity tests are a widely used and established method in research. In laboratory environments, work safety is particularly important when working with carcinogenic, mutagenic, or reprotoxic (CMR) substances. When working with cell cultures, minimizing the risk of contamination with CMR substances and protecting the experimenter must be in the foreground of the experimental setup since risk minimization and occupational safety when handling CMR substances are mandatory. To minimize any personnel risk, studies with solid CMR substances should be carried out in a closed system. However, publications on occupational health and safety in laboratory environments in which CMR substances are tested in cell cultures are rare. Therefore, this article presents an easily applicable and safe method for improving work safety for in vitro chemosensitivity tests when working with CMR substances while also taking cell culture hygiene into account. For this purpose, a risk assessment of the test design was carried out, and the steps that were decisive for safety were highlighted. Some user-friendly and easily reproducible elements are presented, which increase the occupational safety of in vitro chemosensitivity assays, especially by reducing the risk of personnel contamination.

Collagen gel droplet-embedded culture drug sensitivity test (CD-DST) predicts the effect of adjuvant chemotherapy on pancreatic cancer.

PURPOSE: We evaluated the clinical effectiveness of collagen gel droplet-embedded culture drug sensitivity tests (CD-DSTs) in predicting the efficacy of adjuvant chemo-therapeutic treatments for pancreatic cancer (PC). METHODS: The clinicopathological characteristics and prognoses of 22 PC patients who underwent CD-DST after pancreatectomy at Tohoku University between 2012 and 2016 were analyzed retrospectively. Eligibility criteria were resectable or borderline resectable PC, successful evaluation for 5-fluorouracil sensitivity by CD-DST, treatment with S-1 adjuvant chemotherapy, and no preoperative chemotherapy. RESULTS: The rate of successful evaluation by CD-DST was 52.3% in PC. The optimal T/C ratio, defined as the ratio of the number of cancer cells in the treatment group (T) to that in the control group (C), for 5-fluorouracil was 85% using receiver operating characteristic curve analysis. The sensitive group (T/C ratio < 85%; n = 11) had a better recurrence-free survival rate than the resistant group (T/C ratio ≥ 85%; n = 11; P = 0.029). A Cox proportional hazards regression model demonstrated that sensitivity to 5-fluorouracil was an independent predictor of recurrence on multivariate analysis (hazard ratio 3.28; 95.0% CI 1.20-9.84; P = 0.020). CONCLUSIONS: CD-DSTs helped to predict PC recurrence after S-1 adjuvant chemotherapy.

Predictive value of in vitro methyl thiazolyl tetrazolium assay chemosensitivity test of cytotoxic drug activity in breast cancer / 中国综合临床

Objective To investigate the value of methyl thiazolyl tetrazolium assay ( MTT) in predicting drug sensitivity of breast cancer cells in vitro. Methods From January 2010 to July 2016,one hundred and ninety-two patients with breast cancer who underwent modified radical mastectomy or breast conserving surgery (no preoperative radiotherapy or chemotherapy) in the Shanghai Fengxian District Central Hospital were selected. MTT method was used to determine the inhibitory level and sensitivity of 12 drugs and 3 chemotherapy regimens to primary cultured cancer cells of 192 patients with breast cancer. Results (1) The sensitivity of breast cancer cells to 12 drugs were in sequence from high to low as follows: Paclitaxel (PTX)＞ Epirubicin ( EPI )＞ Cisplatin ( DDP )＞ 5-Fluorouracil ( 5-FU )＞ Mitoxantrone ( MIT )＞Vincristine ( VCR )＞ Pirarubicin ( THP )＞ Isosophosphamide ( IFO )＞ Carboplatin ( CBP )＞Cyclophosphamide ( CTX)＞ Methotrexate ( MTX)＞ Changchun Rui bin ( NVB) . The sensitivity of chemotherapy regimens in the three groups from high to low was docetaxel/doxorubicin/cyclophosphamide (TAC )＞cyclophosphamide/epirubicin/fluorouracil ( CEF )＞cyclophosphamide/methotrexate/fluorouracil (CMF). The sensitivity rates of PTX,EPI and DDP were 54%(104/192),42%(81/192) and 37%(71/192) respectively. (2) The average inhibitory rates of DDP,CBP and MIT in stage III breast cancer was higher than those in stage I and II breast cancer,and the differences were statistically significant ( F＝11. 14,4. 303,3. 182,P＜0. 05). (3) HR-breast cancer is more sensitive than HR+breast cancer,PTX, EPI,THP,MIT in HER-2(+) breast cancer is more sensitive than in HER-2(－) breast cancer. Conclusion As a widely used drug sensitivity test method, MTT assay has a certain reference value for screening sensitive drugs and selecting clinical chemotherapy regimens in neoadjuvant chemotherapy of breast cancer. PTX,EPI and DDP are more sensitive to other breast cancer cells than other drugs. Chemotherapy based on in vitro susceptibility results improves the efficiency of chemotherapy and decreases the proportion of changes in chemotherapy schemes due to inefficiency.

Impact of in vitro chemosensitivity test-guided platinum-based adjuvant chemotherapy on the surgical outcomes of patients with p-stage IIIA non-small cell lung cancer that underwent complete resection.

The impact of in vitro chemosensitivity test-guided platinum-based adjuvant chemotherapy on the surgical outcomes of patients undergoing complete resection for locally advanced non-small cell lung cancer (NSCLC) has yet to be elucidated. In the present study, the utility of adjuvant chemotherapy based on the collagen gel droplet embedded culture drug sensitivity test (CD-DST) in patients with p (pathology)-stage IIIA NSCLC was retrospectively analyzed. A series of 39 patients that had received platinum-based adjuvant chemotherapy following complete resection between 2007 and 2012 were enrolled. Their surgical specimens were subjected to the CD-DST. The patients were subsequently classified into two groups on the basis of in vitro anti-cancer drug sensitivity data obtained using the CD-DST: The sensitive group (25 patients) were treated with regimens including one or two of the anti-cancer drug(s) that were indicated to be effective by the CD-DST, whereas the non-sensitive group (14 patients) were treated with chemotherapy regimens that did not include any CD-DST-selected anti-cancer drugs. There were no significant differences in the background characteristics of the two groups [including in respect of the pathological TN (tumor-lymph node) stage, tumor histology, epidermal growth factor receptor mutation status, the frequency of each chemotherapy regimen, and the number of administered cycles]. The 5-year disease-free survival (DFS) rate of the sensitive group was 32.3%, whereas that of the non-sensitive group was 14.3% (P=0.037). In contrast, no difference in overall survival (OS) was observed (P=0.76). Multivariate analysis revealed that adjuvant chemotherapy based on the CD-DST had a significant favorable effect on the DFS (P=0.01). Therefore, the present study has demonstrated that CD-DST data obtained from surgical specimens aid the selection of effective platinum-based adjuvant chemotherapy regimens for patients undergoing complete resection for p-stage IIIA NSCLC. The use of CD-DST-guided platinum-based regimens may have a beneficial impact on the DFS of such patients.

Exploratory phase II trial in a multicenter setting to evaluate the clinical value of a chemosensitivity test in patients with gastric cancer (JACCRO-GC 04, Kubota memorial trial).

BACKGROUND: Although postoperative adjuvant chemotherapy with S-1, an oral fluoropyrimidine, has become a standard of care for gastric cancer in Japan, nonresponders may suffer from the cost and adverse reactions without clinical benefit. This multicenter exploratory phase II trial was conducted to see whether a chemosensitivity test, the collagen gel droplet embedded culture drug sensitivity test (CD-DST), can adequately select patients for chemotherapy. METHODS: The CD-DST using four different concentrations of 5-fluorouracil was conducted with resected specimens from preregistered patients who underwent gastrectomy with D2 or more extensive lymphadenectomy. Patients who were histopathologically confirmed to have stage II or greater disease without distant metastasis were eligible for final enrollment. All patients underwent protocol-specified adjuvant chemotherapy with S-1. Three-year relapse-free survival was compared between patients determined as sensitive by the CD-DST (responders) and those deemed insensitive (nonresponders). Appropriate cutoff values for in vitro growth inhibition were defined when the hazard ratio for relapse in responders and the log-rank P values were at their minimum. RESULTS: Of the 311 patients enrolled, 14 were ineligible and 27 failed to start the protocol treatment. The CD-DST failed in 64 other patients, and survival analyses were conducted with the remaining 206 patients (39 stage II disease, 155 stage III disease, and 12 stage IV disease). The outcome of patients who were determined to be responders was significantly superior to that of nonresponders regardless of the 5-fluorouracil concentrations, although no differences in clinicopathologic characteristics were observed between the two groups, except for age. CONCLUSIONS: The CD-DST identified those who benefit from adjuvant chemotherapy. It deserves further evaluation in the setting of a prospective randomized trial. ClinicalTrials.gov identifier: NCT00287755.

Evaluation on the chemosensitivity of hepatocellular carcinoma during mimetic transcatheter arterial embolization / 中华肝胆外科杂志

Objective To investigate whether 5 different chemotherapeutic drugs and their combination of either two drugs could further promote the inhibition on the cell growth of HCC cell line (HepG2) in vitro in the hypoxic and hyponutritional culture medium (HHCM) mimicking the different scenarios of transcatheter arterial chemoembolization (TACE).Methods The cells were treated by 5 drugs for 2 h, 4 h,6 h and 24 h, which include epirubicin (EPI), cisplatin (DDP), mitomycin-C (MMC), oxaliplatin (OXA) and 5-fluorouracil (5-FU) in four concentrations of HHCM (5％, 10％, 25％ and 50％) mimicking the scenarios during TACE and the cell viability was assessed using 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay.The combinations of dual drugs treated for 24 h were also tested.Results The sensitive drugs with inhibition rates more than 30％ were EPI, MMC and OXA in 4 different concentrations of HHCM.The sensitivity of the drugs treated for 24 h was significantly increased compared with that for 2 h in 5％, 10％ and 25％ HHCM.The dual combinations did not increase the chemosensitivity of HepG2 cells.Conclusions EPI, MMC and OXA exhibited cytotoxic activity against HepG2 cells in various hypoxia and hyponutrition states.Prolonging the exposure time could increase the sensitivity of drug in HHCM, and the combination of dual drugs cannot enhance the cytotoxic effect.

Cytotoxic activity of anticancer drugs on hepatocellular carcinoma cells in hypoxic-hyponutritional culture.

To investigate which anticancer drugs and combination of dual drugs could further promote the inhibition of cell growth in vitro against HCC cell line (HepG2) in the hypoxic and hyponutritional culture medium (HHCM) mimicked the different scenarios of transcatheter arterial chemoembolization (TACE). The cells of hepatocellular carcinoma (HCC) treated by TACE suffered various hypoxia and hyponutrition. The cells were treated for 2 hours, 4 hours, 6 hours, and 24 hours, respectively, using 10 drugs including epirubicin (EPI), cisplatin (DDP), mitomycin-C (MMC), oxaliplatin (OXA), hydroxycamptothecin (HCPT), 5-fluorouracil (5-FU), gemcitabine (GEM), docetaxel (DTX), thiotepa (TSPA), and pemetrexed disodium (PEM) in 4 concentrations of HHCM (5%, 10%, 25%, and 50%, respectively) mimicking the scenario of TACE and were assessed using 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay. The cells treated with combinations of dual drugs for 24 hours were also tested. The sensitive drugs with inhibition rates more than 30% were EPI, MMC, HCPT, OXA, and PEM in 4 types of HHCMs. The sensitivity of the cells to treatment with drugs for 24 hours was significantly higher than the sensitivity of the cells to treatment with drugs for 2 hours in 5%, 10%, and 25% HHCM. The sensitivity of the combination of dual drugs was no more than the sensitivity of the single drug with higher sensitivity in 4 concentrations of HHCM. EPI, MMC, HCPT, OXA, and PEM exhibited cytotoxic activity against HepG2 cells in various hypoxia and hyponutrition states. Prolonging the time of exposure could increase the sensitivity of drug, and the combination of dual drugs cannot enhance the cytotoxic effect.

Differences in chemosensitivity between primary and paired metastatic lung cancer tissues: In vitro analysis based on the collagen gel droplet embedded culture drug test (CD-DST).

BACKGROUND: To elucidate the differences in chemosensitivity to anticancer drugs between primary and metastatic lesions in non-small cell lung cancer (NSCLC) patients, we examined the in vitro chemosensitivities of surgically resected NSCLC tissues. METHODS: A total of 32 specimens were enrolled: 26 specimens of primary lesions paired with metastases in the lymph node, 3 specimens of primary lesions paired with metastases in the adrenal gland, and 3 specimens of primary lesions paired with metastases in the lung. The collagen gel droplet embedded culture drug test (CD-DST) was applied to examine the sensitivity of the tissues to anticancer drugs, including cisplatin, gemcitabine, vinorelbine, docetaxel and 5-fluorouracil. RESULTS: The degree of in vitro sensitivity to each anticancer drug varied between the primary and metastatic lesions. The sensitivity of the paired metastatic lesions was significantly lower than that of the primary lesions only for gemcitabine (P=0.029), vinorelbine (P=0.012), and docetaxel (P=0.009). The incidence of cases diagnosed as CD-DST-sensitive among the paired metastatic lesions was significantly lower than that for the primary lesions for vinorelbine (P=0.035) or docetaxel (P=0.022). The difference in the sensitivity to gemcitabine between the primary and paired non-lymphatic metastases was clearer than that between the primary lesion and paired lymph node metastases. CONCLUSIONS: The sensitivities of the paired metastatic lesions to some anticancer drugs were significantly lower than those of the primary lesions. When performing chemotherapy based on CD-DST data using primary tumors from patients with postoperative recurrence, an appropriate regimen can be selected by carefully considering these differences.

Study on chemosensitivity test in vitro between peripheral blood lymphocytes and tumor cells in elderly lung cancer / 中国基层医药

Objective To explore the correlation of chemosensitivity in vitro of anti-cancer drugs between peripheral blood lymphocytes and tumor cells in non-small cell lung cancer of elderly patients.Methods The MTT method was used to test the sensitivity of the peripheral blood lymphocyte and the tumor cells of 52 patients with nonsmall cell lung cancer to 13 kinds of anti-cancer drugs.Results The sensitivity test in eleven drugs include CDDP,CBP,LOHP,PTX,CTX,ICTX,THP,VP-16,GEM,VCR and NVB in the peripheral blood lymphocyte were associated with that in the tumor cells.But no dependablity in two drugs,ADM and HCPT.Conclusion The peripheral blood lymphocytes could be replace tumor cells to test the chemosensitivity of anti-cancer drugs in patients with non-small cell lung cancer.

Research actuality of chemosensitivity testing in chemotherapy / 国际外科学杂志

This paper explains the research status of chemotherapy sensitivity test in three aspects of history of development, specific methods and clinical application. Chemotherapy sensitivity test is an important way to achieve individual treatment of cancer, after more than 60 years, there are two major categories(in vivo method and in vitro method) of more than 10 kinds of methods. The basic steps of sensitivity test inelude culture of primary tumor cells, chemotherapy drugs mixed, the reaction mixture, observing the results of detection and analysis of indicators. This paper focuses on basic principles, main steps and characteristics of six methods, such as the renal capsule of nude mice model of human cancer, the difference between staining cell, tetrazolium salt colorimetric, adenosine triphosphate based bioluminescence tumor chemosensitivity assay, collagen gel embedded culture method and targeting molecule sensitivity assay. Through the results of several clinical trials, it can be seen that chemotherapy under the guidance of drug sensitivity test significantly improved more than experience chemotherapy in efficient rate, median progression-free survival time, survival time, clinical complete remission rate, pathological complete remission rate, etc.

A study on chemosensitivity test in relation with the phases of cell cycle in ovarian cancer cell line / 대한산부인과학회지

OBJECTIVE: Theoretically, chemotherapy sensitivity and resistance assays help to predict which sensitive agent will be effective for patients. Due to low correlation between in vitro assay results and in vivo responses, chemosensitivity test is not generally applied in actual clinical practices. The aim of this study is to evaluate the influence of cell cycle in the course of cell culture stage on chemosensitivity test as a disturbing factor. METHODS:After synchronization at G0, we conducted experiments on SKOV-3 cell line according to determined cell cycle span (G0, G0/G1, S, G2/M) with MTT (methylthiazolyl-diphenyl- tetrazolium bromide) chemosensitivity test. We evaluated the sensitivity changes of six chemotherapeutic agents (5-FU, Etoposide, Cisplatin, Topotecan, Paclitaxel, Doxorubicin) in each phase at target times. RESULTS: Each phase represented the various results of MTT sensitivity on six chemotherapeutic agents. The variation of sensitivity between experimental (cell cycle synchronized culture) group and reference (conventional culture) group was 21.3+/-5.1 (mean+/-.D)%. CONCLUSION: The cells in the each phase of cell cycle represent different levels of sensitivity to the same chemotherapeutic agent. The required cell culture stage of chemosensitivity test can blur the true candidate agent. This finding can be regarded as one of the reasons of mismatch between in vitro chemosensitivity and in vivo response of candidate chemotherapeutic agents.

A study on chemosensitivity test in relation with the phases of cell cycle in ovarian cancer cell line / 대한산부인과학회지

OBJECTIVE: Theoretically, chemotherapy sensitivity and resistance assays help to predict which sensitive agent will be effective for patients. Due to low correlation between in vitro assay results and in vivo responses, chemosensitivity test is not generally applied in actual clinical practices. The aim of this study is to evaluate the influence of cell cycle in the course of cell culture stage on chemosensitivity test as a disturbing factor. METHODS:After synchronization at G0, we conducted experiments on SKOV-3 cell line according to determined cell cycle span (G0, G0/G1, S, G2/M) with MTT (methylthiazolyl-diphenyl- tetrazolium bromide) chemosensitivity test. We evaluated the sensitivity changes of six chemotherapeutic agents (5-FU, Etoposide, Cisplatin, Topotecan, Paclitaxel, Doxorubicin) in each phase at target times. RESULTS: Each phase represented the various results of MTT sensitivity on six chemotherapeutic agents. The variation of sensitivity between experimental (cell cycle synchronized culture) group and reference (conventional culture) group was 21.3+/-5.1 (mean+/-.D)%. CONCLUSION: The cells in the each phase of cell cycle represent different levels of sensitivity to the same chemotherapeutic agent. The required cell culture stage of chemosensitivity test can blur the true candidate agent. This finding can be regarded as one of the reasons of mismatch between in vitro chemosensitivity and in vivo response of candidate chemotherapeutic agents.

Collagen gel droplet-embedded culture drug-sensitivity test and potential for personalizing cancer treatment.

Sensitivity testing for general anticancer agents involves culturing cancer cells, exposure to an anticancer agent, and assessing the degree of growth inhibition. One such method is the collagen gel droplet-embedded culture drug-sensitivity test (CD-DST). Clinical results confirm a close correlation of a better than 75% accuracy between CD-DST results and responses to anticancer agents administered in the clinical setting. Although there have been few randomized, controlled studies of the CD-DST method, the general observation is that cancer patients survive longer if their disease responds to an anticancer agent than if it is ineffective. Therefore, it can be extrapolated that the high diagnostic accuracy of CD-DST is indirect evidence that this method can be used to select the group for whom chemotherapy will be effective, with a resultant prolongation of their survival time, and the group for whom chemotherapy will be ineffective, with no increased survival time.

In-vitro Chemosensitivity Test for Colorectal Cancer using an Adenosine-triphosphate-based Chemotherapy Response Assay (ATP-CRA)

Purpose: The adenosine-triphosphate-based chemotherapy response assay (ATP-CRA) is a well-documented and validated technology for individualizing chemotherapy in cancer patients. We evaluate the feasibility of ATP-CRA in colorectal cancer patients. This study will illustrate the assay's success rate, the mean coefficient of variation, and the turnaround time as a validation tool for a chemosensitivity test. Methods: A total of 118 patients, treated by surgery between June 2004 and September 2005 were evaluated for chemosensitivity to seven anticancer agents (5-fluorouracil (5-FU), oxaliplatin, irinotecan, epirubicin, etoposide, gemcitabine, and paclitaxel) by using an ATP-CRA. To allow a comparison between samples, we calculated the chemosensitivity index (CI) based on the percentage cell death rate (CDR, %) at each test drug concentration. Results: The assay success rate was 85.5% (118/138), and the mean coefficient of variation, indicating intra-assay error level, was 9.2%. CDR measured at a therapeutic peak plasma concentration ranged from 0% to 93.6% with a median of 31.0% for 5-FU, 28.5% for oxaliplatin, 34.0% for irinotecan, 25.0% for epirubicin, 21.0% for etoposide, 22.0% for gemcitabine, and 25.2% for paclitaxel. According to the CI, the most sensitive drug varied from patient to patients 10.9% for 5-FU, 10.9% for oxaliplatin, 24.7% for irinotecan, 11.8% for epirubicin, 22.4% for etoposide, 1.1% for gemcitabine, and 23.3% for paclitaxel. Conclusions: Our data suggest that the ATP- CRA is a feasible in-vitro chemosensitivity test in colorectal cancer and that patients show heterogeneous chemosensitivity. A study evaluating the predictive value of ATP-CRA directed therapy is needed to determine the clinical usefulness of the test.

Multi-Disciplinary Treatment of a Rare Pelvic Cavity Ependymoma

Ependymomas usually develop from neuroectodermal organs. Here, we present an ependymoma arising from the pelvic cavity. A 27-year-old Korean female was admitted to the hospital with a sensation of abdominal fullness. Imaging studies revealed a huge heterogeneous nodular mass in the pelvis and lower abdomen. Laparotomy showed that two large masses with multiple nodules were located between the uterus and rectum and uterus and bladder, respectively. Histologically, the tumor was characterized by compact columnar neoplastic cells divided by fibrovascular septae. The neoplastic cells formed true ependymal rosettes and perivascular pseudorosettes. Immunohistochemical staining showed a strong positive reaction for glial fibrillary acidic protein (GFAP) and vimentin and a partial positive reaction for S100 and EMA. The tumor was thus diagnosed as an ependymoma arising from the pelvic cavity. The patient was treated with a debulking operation and chemotherapy based upon the in vitro chemosensitivity test results. The patient was free of cancer for 4 years following surgery. This is a rare case of extraneural ependymoma for which an in vitro chemosensitivity test was critical in determining the multidisciplinary approach for treatment.

Multi-Disciplinary Treatment of a Rare Pelvic Cavity Ependymoma

Ependymomas usually develop from neuroectodermal organs. Here, we present an ependymoma arising from the pelvic cavity. A 27-year-old Korean female was admitted to the hospital with a sensation of abdominal fullness. Imaging studies revealed a huge heterogeneous nodular mass in the pelvis and lower abdomen. Laparotomy showed that two large masses with multiple nodules were located between the uterus and rectum and uterus and bladder, respectively. Histologically, the tumor was characterized by compact columnar neoplastic cells divided by fibrovascular septae. The neoplastic cells formed true ependymal rosettes and perivascular pseudorosettes. Immunohistochemical staining showed a strong positive reaction for glial fibrillary acidic protein (GFAP) and vimentin and a partial positive reaction for S100 and EMA. The tumor was thus diagnosed as an ependymoma arising from the pelvic cavity. The patient was treated with a debulking operation and chemotherapy based upon the in vitro chemosensitivity test results. The patient was free of cancer for 4 years following surgery. This is a rare case of extraneural ependymoma for which an in vitro chemosensitivity test was critical in determining the multidisciplinary approach for treatment.

A feasibility study of adenosine triphosphate-based chemotherapy response assay (ATP-CRA) as a chemosensitivity test for lung cancer.

PURPOSE: A chemosensitivity test can reflect the differences in responses of individual cancer patients to chemotherapeutic agents. The adenosine triphosphate-based chemotherapy response assay (ATP-CRA) is an accurate method, which does not require a large amount of tissue specimen. So far, no studies have evaluated the utility of the ATP-CRA in Korea. Therefore, we investigated the clinical usefulness of the ATP-CRA in 53 patients with lung cancer. MATERIALS AND METHODS: Tumor tissues were obtained from bronchoscopic biopsies or surgical resections. The validity of ATP-CRA was assessed focusing on the success rate, experimental error level (intraassay mean coefficient of variation [CV]) and reproducibility. RESULTS: The overall success rate of ATP-CRA was 90.6% (48/53). Normal cells were effectively eliminated from the tumor tissues with the use of ficoll gradient centrifugation and immunomagnetic separation, which was confirmed using loss of heterozygosity analysis of the 3p deletion. The mean CV of ATP assays was 10.5+/-4.6%. The reproducibility of ATP assays was 94+/-3.8%. The results of the ATP assays were reported to physicians within 7 days of specimen collection. More than 6 anticancer drugs were tested on the tumor specimens obtained from bronchoscopic biopsies. CONCLUSION: The ATP-CRA is a stable, accurate and potentially practical chemosensitivity test in patients with lung cancer.

A Feasibility Study of Adenosine Triphosphate-based Chemotherapy Response Assay (ATP-CRA) as a Chemosensitivity Test for Lung Cancer / Journal of the Korean Cancer Association, 대한암학회지

PURPOSE: A chemosensitivity test can reflect the differences in responses of individual cancer patients to chemotherapeutic agents. The adenosine triphosphate-based chemotherapy response assay (ATP-CRA)is an accurate method, which does not require a large amount of tissue specimen. So far, no studies have evaluated the utility of the ATP-CRA in Korea. Therefore, we investigated the clinical usefulness of the ATP-CRA in 53 patients with lung cancer. MATERIALS AND METHODS: Tumor tissues were obtained from bronchoscopic biopsies or surgical resections. The validity of ATP-CRA was assessed focusing on the success rate, experimental error level (intraassay mean coefficient of variation [CV]) and reproducibility. RESULTS: The overall success rate of ATP-CRA was 90.6% (48/53). Normal cells were effectively eliminated from the tumor tissues with the use of ficoll gradient centrifugation and immunomagnetic separation, which was confirmed using loss of heterozygosity analysis of the 3p deletion. The mean CV of ATP assays was 10.5+/-4.6%. The reproducibility of ATP assays was 94+/-3.8%. The results of the ATP assays were reported to physicians within 7 days of specimen collection. More than 6 anticancer drugs were tested on the tumor specimens obtained from bronchoscopic biopsies. CONCLUSION: The ATP-CRA is a stable, accurate and potentially practical chemosensitivity test in patients with lung cancer.

The Reliability of Histoculture Drug Response Assay (HDRA) in Chemosensitivity Tests for Breast Cancer.

PURPOSE: Cancers are highly individual in their response to chemotherapy, however attempts to predict tumor response to drugs using in vitro cell culture have largely failed. A new technology, the histoculture drug response assay (HDRA), appears to have solved many previous problems. The purpose of this study is to evaluate the reliability of HDRA in a chemosensitivity test for breast cancer. MATERIALS AND METHODS: Tumor specimens from breast cancer patients were evaluated by HDRA using different chemotherapeutic agents. Each specimen was tested using a blind method in order to determine the reproducibility of HDRA results for the same tissue and with a triplicated assay in order to determine reproducibility by different examiners. The evaluative power of this assay and the chemosensitivity of drugs for each specimen was determined. RESULTS: Specimens of 92.9% (65/70) were successfully cultured and evaluated for chemosensitivity. The reproducibility of HDRA for the same tissue was 75% (100% agreement) and 100% (over 70% agreement), respectively. And the reproducibility by different examiners was 78.9% (100% agreement) and 94.7% (over 70% agreement), respectively. Each specimen demonstrated a response to at least one agent. CONCLUSION: The evaluative power and reproducibility of HDRA were high, therefore it might serve as a reliable clinical method for chemosensitivity testing. However, there is a need for clinical trial in which patients are initially randomized for treatment either by HDRA direction or by clinician's choice.